The development of breast cancer can be modulated by actions of the immune system. Reciprocally, tumors appear to cause profound alterations of the immunologically relevant cells either directly, via tumor cell derived factors, or in an indirect manner. Dr. Lopez proposes to continue studies using the well-characterized murine mammary tumor model to elucidate the interactions between the growing neoplasms and the immune effector cells. The DI -DMBA-3 tumor, and the DA-3 tumor cell line derived in vitro from the former, are syngeneic to BALB/c mice and grow in vivo in the host of origin. She will focus especially on elucidating the phenotypic and functional alterations observed in the T cell compartment of tumor bearing mice. The aims are to (1) delineate the interactions between thymocytes and the thymic microenvironment leading to thymic involution during mammary tumorigenesis; (2) analyze the basis of down-regulation of IEL-12 production by macrophages and the altered T cell responsiveness to this cytokine in the tumor bearing mice; (3) elucidate the molecular events leading to the over-expression of matrix metalloproteinase-9 (MMP-9) in T cells from tumor bearers and its role in the infiltration of these lymphocytes into mammary tumors; and (4) determine the mechanisms by which DA-3 mammary tumor cells transfected with a secreted form of the human MUCI gene fail to grow in intact BALB/c mice, while they develop in immunodeficient mice. An under- standing of the causes for the immune deviations occurring during mammary tumorigenesis, at the cellular and molecular levels, will help devise rational new therapeutic approaches for the eventual control of breast cancer.